We propose to study the action of endotoxin at the cellular level using two model systems. 1) the mitogenic effect of endotoxin on mouse B-lymphocytes and 2) the cytotoxic effect of endotoxin on mouse macrophages. We will time the events of LPS induced mitogenesis, i.e. initiation of DNA, RNA and protein synthesis and then concentrate our efforts on events prior to these, i.e. cell binding of LPS, internalization of LPS, and on membrane phenomena, i.e. pinocytosis, glucose-transport, phospholipid turnover, and alterations in cyclic AMP. We will characterize the toxic effects of LPS on macrophages from normal, tolerant and hyperreactive mice by light and electron microscopy and histochemistry and look for a secondary toxicity on bystander cells.